The Laser Microbeam and Medical Program (LAMMP) is a NIH Biomedical Technology Resource Center dedicated to the use of lasers and optics in biology and medicine. LAMMP is located within the Beckman Laser Institute (BLI), an interdisciplinary biomedical research, teaching, and clinical facility at the University of California, Irvine. The BLI functions administratively as a division within the Department of Surgery in the Medical School at UC Irvine. Overall resource objectives are to promote a well-balanced Center with activities in technological research and development, collaborative/service research, and training/dissemination. In this fifth renewal application of LAMMP, we emphasize our unique capabilities to facilitate "translational" research by rapidly moving basic science and technology discoveries from "benchtop to bedside". This is accomplished by combining state of the art optical technologies with our in-house facilities in cellular and tissue engineering, animal models, and human subjects. LAMMP provides both Microbeam and Microscopy Technologies (MMT) for optical manipulation and functional imaging of living cells and tissues, and Medical Translational Technologies (MTT) for monitoring, treating, and imaging pre-clinical animal models and human subjects. A total of six new technology research and development projects are proposed that will result in the construction of 5 new, dedicated instruments. MMT and MTr technologies am linked together by a common set of optical technologies, computational models, data visualization methods, and biomedical applications. Combined, they are capable of characterizing and imaging structure and biochemical composition in tissues with scalable resolution and depth sensitivity ranging from microns to centimeters. This allows selective interrogation of the essential components of tissue: molecules, cells, extracellular matrix, and vasculature. Throughout the grant cycle, we will apply these emerging methods to biological models and clinical problems in order to characterize and quantify the precise structural and functional origins of intrinsic optical signals. Our long-term goal is to advance these technologies so they become widely-available, enabling methods for solving fundamentally important problems in biology and medicine.